1. Field of the Invention
The present invention relates to an apparatus and method to aspirate and dispense precise volumes of liquid, and more specifically to an apparatus and method to report a variety of types of information regarding apparatus performance or usage. The apparatus includes a signal transmitting device and an optional signal detecting device.
2. Description of the Prior Art
Many analysis methods used in biological, biotechnological, pharmaceutical, chemical and other types of research laboratories require accurate measurement and dispensing of small volumes of liquids that can range from one nanoliter to several milliliters. In one application, small volumes of liquid may be aspirated or dispensed from liquid handling devices having a single delivery channel or multiple channels configured to deliver or aspirate liquid simultaneously or sequentially. Specific examples include handheld single- or multi-channel pipettes, configured to deliver or aspirate liquid samples from 1, 8 or 12 channels at a time, and automated delivery equipment configured to deliver or aspirate 96 or 384 liquid samples at one time.
In general, liquid handling devices, which also may be called pipettes, are syringes, each including a cylinder extended by a shaft or channel, and a liquid holding tip and a piston to slide within the cylinder. The piston may be activated manually or automatically by a motor over a selectable travel distance. The travel distance may be regulated manually or automatically using a computer. The use of liquid handling devices to aspirate and dispense precise volumes of liquids is well known. Also well known is the use of replaceable disposable tips to permit the sequential use of such devices in the handling of different liquids without contamination.
Replaceable tips are commonly formed from plastic and are a hollow, conical frustum with two open ends, one for mating with the shaft of the liquid handling device, and the other to permit liquid flow into and out of the interior of the tip.
For liquid handling devices, the level of aspiration and/or delivery must be both accurate and precise. At any given time the handling device may not be functioning within the requirements of the process or the specifications of the manufacturer. Many factors contribute to inaccuracy and imprecision of the liquid delivery and aspiration. For this reason it is necessary to repeat exactly procedures from one delivery and/or aspiration to the next to ensure correct operation and the integrity of the analysis. Therefore, the manufacturer must assure that the device functions correctly at the time of the analysis.
When using an air-displacement pipette specifically to aspirate liquid for quantitative delivery, it is important that the operator insert the tip to the correct depth in the liquid from which the aliquot is to be taken. An analysis of the importance of holding the tip at a proper depth within a liquid sample prior to aspiration is provided in International Organization for Standardization (ISO) standard, ISO 8655-2, dated 10 Oct. 2002. Additionally, under ISO standard 8655-6, dated 10 Oct. 2002, a typical tip insertion depth for aspiration should be 2-3 mm. Both ISO 8655-2 and ISO 8655-6 are incorporated herein by reference. Depending on the ambient light, on the angle of observation, on the optical density of the liquid being aspirated, and on the skill and visual acuity of the operator, this degree of accuracy can be difficult or impossible to achieve. If the insertion depth is incorrect, then the amount of liquid aspirated by the pipette will be incorrect. According to ISO 8655-2, the error in aspirated volume due to improper insertion depth can be up to 1%, well outside of the manufacturer's specified tolerance of many pipettes, typically less than 0.5%. It therefore would be desirable to develop a pipette and associated disposable tip that provide a visual aid to permit an operator to clearly see when the tip is inserted to the correct depth in the source liquid.
The same concerns apply to liquid aspiration by an automated (robotic) liquid handling device. With automated liquid handling devices, the function of sensing the correct insertion depth optimally is performed by a feedback sensor. The feedback sensor provides a signal to a control mechanism, which then directs the automated device to lower the tip until it is immersed to the correct depth. Where liquid aliquots are taken repeatedly from the same source vessel, the tip also must be repeatedly inserted more deeply into the vessel after each aspiration and before the next to maintain the correct insertion depth. An insertion-depth detection mechanism will accomplish this automatically to allow more accurate and reproducible liquid delivery by the automated liquid handler.
Another specific concern regarding the performance of liquid handling devices is the correct dispensing of liquid from the tip into the receiving vessel. If the tip is situated above the surface of liquid in the receiving vessel when liquid is dispensed (free-air or dry dispense), then surface tension of the liquid in the tip will often prevent all of the liquid from being discharged out of the tip. If the tip is held too deeply into the liquid in the receiving vessel (wet-dispense), then liquid may adhere to the outside of the tip and be inadvertently carried out when the tip is withdrawn. Finally, if an extra measure of air is dispensed to “blow out” any residue of liquid from within the tip, that air can form a bubble inside the liquid in the receiving vessel. Such bubbles generally aggregate on the side or bottom of the receiving vessel. Such a bubble is likely to lead to error when making an optical absorbance or emission reading. This latter effect especially is a problem when liquid is being dispensed into a microtiter plate because of the sample size and relative proportionate size of the bubble. Prior to dispensing an aliquot therefore, an automated liquid handler preferably should lower the tip until it touches, or is just below the surface of, the liquid in the receiving vessel.
What is needed therefore is a liquid handling device including one or more apparatus capable of detecting one or more of a multiplicity of parameters. These parameters include: (1) whether a tip is properly attached to a particular channel of the liquid handler; (2) that the proper type of tip is connected to the liquid handler; (3) the point at which the tip contacts the liquid surface, both when it is empty, for aspiration purposes, and when it is full, for dispensing purposes; (4) the point at which the tip's immersion depth in a liquid is proper, within an acceptable range for the particular pipette and tip design; (5) that liquid is present in the tip, after it has been withdrawn from the source vessel, to verify that aspiration has successfully taken place; and (6) that residual liquid is not present in the tip after dispensation is complete and after the tip is withdrawn from the receiving vessel, to verify that dispensation has successfully taken place.